Pharmacologic Actions of Proton Pump Inhibitors and Acid Pump Antagonists; Implication in the Treatment of Helicobacter pylori-associated Gastric Diseases
Korean J Helicobacter Up Gastrointest Res 2005;5(2):113-123
Published online December 3, 2005
© 2005 Korean College of Helicobacter and Upper Gastrointestinal Research.

Marie Yeo, Ph.D., Misun Kwak, Ph.D., In-Sik Chung, M.D., Ph.D.*, In Suh Park, M.D., Ph.D., Kee-Myung Lee, M.D., Kwang Jae Lee, M.D. and Ki-Baik Hahm, M.D.,

Department of Gastroenterology and Genome Research Center of Gastroenterology, Ajou University School of Medicine, Suwon, Department of Gastroenterology, Kangnam St. Mary's Hospital, The Catholic University of Korea*, Seoul and Department of Gastroenterology, Ilsan Hospital, Ilsan, Korea
Abstract
Since the acid related diseases such as duodenal and gastric ulcer, reflux esophagitis, and gastritis, have bothered human throughout recorded history, the development of anti-secretory agents including PPIs (proton pump inhibitors) and H2-RAs (histamine type 2 receptor antagonists) revolutionized the second millennium and at the beginning of the third millennium, we are able to control acid secretion at will and can remove the responsible bug for dyspepsia in the stomach. Though the design of small ligand antagonists for acid secretion is not so easy, at least the structure of the natural ligand provides a template for such molecules, that is, ATP and hydronium ion (H3O+) on the cytoplasmic side and K+ on the luminal side. A compound competing with ATP in cell cytoplasm would obviously be nonspecific and molecules to act as H3O- surrogates necessitate some lag times for action and disadvantage of irreversibility and risk of carcinogenesis. Similar considerations applying to design of compounds substituting K+ on the outside surface led to the development of acid pump antagonists (APAs), of which advantages are independent of secretory status, no lag time required, reversible in actions, and could be therapeutic antacids, allowing "on- demand dosage. Our recent studies also revealed that APA seems to be superior against Helicobacter pylori infection, based on the findings that they exerted significant anti-inflammatory, gastroprotective, and overt molecular actions. Conclusively, in the current review, we described the development of the discovery of gastric acid secretion, gastric acid pump, the biology of acid related diseases, inhibition of gastric acid pump, and molecular actions of APA against H. pylori infection. APA could be extensively applied to either acid related diseases or inflammatory related gastric diseases. (The Korean Journal of Helicobacter and Upper Gastrointestinal Research 2005;5:113-123)
Keywords : Gastric acid secretion, Acid pump, Helicobacter pylori, Proton pump inhibitor, Acid pump antagonist


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